HIV-infected injection drug users (IDUs) represent a marginalized population with substantial disparities in health care access and outcomes. Since 1988, the AIDS Linked to the Intravenous Experience (ALIVE) study has followed disadvantaged, predominantly African American HIV-infected and at-risk IDUs in a community-based observational cohort, providing important evidence on the natural and treated course of HIV among IDUs. We have characterized the rates and risk factors for incident HIV infection and for progression to AIDS or death, described patterns of risk behavior, and determined barriers to optimal HIV care. Since availability of effective antiretroviral therapy (ART), optimal HIV care is now achieved by early HIV testing; prompt linkage to HIV care, timely initiation of ART, high adherence, retention in care, and prolonged virological suppression. Drug use may have detrimental effects at each stage of this HIV Care Continuum. Proposed is a multidisciplinary research agenda with the primary objective to continue the epidemiological, pathogenesis, behavioral, and clinical characterization of the evolving HIV epidemic among IDUs as they age and drug use patterns change. While the cohort has and continues to be a platform for an array of studies critical to addressing critical on HIV and drug use, this proposal emphasizes examination of IDUs' navigation of the HIV Care Continuum. We aim to characterize the dynamic nature of the Care Continuum and to identify the key determinants of successful navigation and the consequences of stagnation. Successful navigation entails consistent engagement in care with prompt ART initiation and prolonged viral suppression. In contrast, we introduce the concept of stagnation, incorporating navigation patterns involving a failure to progress and delayed or relapsing transitions through the Continuum. We will describe longitudinal navigation patterns, characterize the time required to transition through stages, and identify sociodemographic, behavioral, provider and neighborhood-level determinants of the primary navigation patterns. We hypothesize that less successful navigation (stagnation) in the Care Continuum will have serious clinical consequences, increasing the risk for both AIDS or non-AIDS events as well as death. The key impact of this aim is to illuminate mechanisms, identify modifiable risk factors, and provide novel insight to inform efficient and targeted intervention development to mitigate the consequences of less effective HIV care among IDUs. To achieve these aims, we continue biannual visits with interview, exam, and biospecimen collection supplemented by medical record review and registry linkage. ALIVE represents the minority, socially-marginalized population at highest risk for HIV progression and limited access to care in Baltimore and nationally. The ALIVE study remains well- positioned to address these emerging issues confronting aging HIV-infected IDUs, namely characterizing long- term outcomes and enhancing HIV care through improving navigation of the HIV Care Continuum.